The present invention relates generally to the field of methods and medical devices for modulating cardiac muscle activity and contractility and for cardiac pacing and more specifically to the field of methods for determining timing of delivery of non-excitatory excitable tissue control (ETC) signals to the heart.
Excitable tissue control (ETC) devices are devices which modulate the activity of excitable tissues by application of non-excitatory electrical field signals to the excitable tissue through suitable electrodes in contact with the tissue. For example, ETC devices may be used, inter alia, to increase or decrease the contractility of cardiac muscle in vitro, in vivo and in situ., as disclosed in detail in PCT application PCT/IL97/00012 (International Publication Number WO 97/25098) to Ben-Haim et al., titled xe2x80x9cELECTRICAL MUSCLE CONTROLLERxe2x80x9d, incorporated herein by reference. Other methods and applications of ETC devices are disclosed in PCT application PCT/IL97/00231 (International Publication Number WO 98/10828) titled xe2x80x9cAPPARATUS AND METHOD FOR CONTROLLING THE CONTRACTILITY OF MUSCLESxe2x80x9d to Ben Haim et al., incorporated herein by reference, PCT application PCT/IL97/00232 (International Publication Number WO 98/10829) titled xe2x80x9cDRUG-DEVICE COMBINATION FOR CONTROLLING THE CONTRACTILITY OF MUSCLESxe2x80x9d to Ben Haim et al., incorporated herein by reference and PCT application PCT/IL97/00233 (International Publication Number WO 98/10830) titled xe2x80x9cFENCING OF CARDIAC MUSCLESxe2x80x9d to Ben Haim et al., incorporated herein by reference, PCT application PCT/IL97/00235 (International Publications Number WO 98/10831) to Ben Haim et al., titled xe2x80x9cCARDIAC OUTPUT CONTROLLERxe2x80x9d, incorporated herein by reference.
Further applications of the ETC including devices combining cardiac pacing and cardiac contractility modulation are disclosed in PCT Application, International Publication No. WO 98/10832, titled xe2x80x9cCARDIAC OUTPUT ENHANCED PACEMAKERxe2x80x9d to Ben Haim et al., co-assigned to the assignee of the present application. Such ETC devices function by applying to selected cardiac segments non-excitatory electrical signals of suitable amplitude and waveform, appropriately timed with respect to the heart""s intrinsic electrical activity or with respect to paced cardiac electrical activity. The contraction of the selected segments can be modulated to increase or decrease the stroke volume of the heart. The timing of the ETC signals must be carefully controlled since application of the ETC signal to the myocardium at inappropriate times may be arrhythmogenic. The ETC signal must therefore be applied to the selected cardiac segment within a defined time interval during which the selected cardiac segment will not be stimulated by the ETC signal.
As disclosed in International Publication No. WO 98/10832, the ETC signal may be timed relative to a trigger signal which is also used as a pacing trigger, or may be timed relative to locally sensed depolarizing electrogram signals.
Timing of the delivery of ETC signals relative to the time of detection of locally sensed electrogram signals may present certain practical problems. For example, triggering of the ETC signal by any locally detected depolarizing signals irrespective of the time of detection of the depolarizing signal within the cardiac beat cycle, may increase the probability of spurious detection of noise signals or of ectopic beats such as premature ventricular contractions (PVCs) or the like, which may lead to delivery of improperly timed and potentially arrhythmogenic ETC signals. It is therefore desirable to have a method for determining proper timing of the delivery of ETC signals without unduly increasing the probability of delivering an improperly timed ETC signal caused by spurious noise detection or by detection of ectopic beats.
There is therefore provided, in accordance with a preferred embodiment of the present invention, a method for timing the delivery of a non-excitatory signal to a heart within a cardiac beat cycle. The method includes the steps of applying electrodes to a plurality of cardiac sites, sensing electrical activity in at least a first site of the plurality of cardiac sites through at least a first electrode of the electrodes for detecting a first electrical depolarization event within the beat cycle, sensing electrical activity in at least a second site of the plurality of sites through at least a second electrode of the electrodes for detecting at least a second electrical depolarization event within the beat cycle, and applying the non-excitatory signal to at least one of the cardiac sites through at least one of the electrodes in response to detecting the second electrical depolarization event within an alert window period. The alert window period starts at a first delay from the time of detection of the first electrical depolarization event and has a first duration. The applying is delayed from the time of detecting of the second electrical depolarization event.
Furthermore, in accordance with another preferred embodiment of the present invention, the method includes the step of inhibiting the applying of the cardiac non-excitatory signal of the step of applying in response to detecting at the second site a third electrical depolarization event preceding the second electrical depolarization event. The third electrical depolarization event is detected within an inhibition window period. The inhibition window period starts at a second delay from the time of detection of the first electrical depolarization event and terminates before or at the time of starting of the alert window period. The second delay is smaller than the first delay.
Furthermore, in accordance with another preferred embodiment of the present invention, the step of inhibiting includes the step of initiating an inhibition refractory period. The inhibition refractory period starts at the time of detecting of the third electrical depolarization event and has a second duration. The sensing of the electrical activity in the second site is disabled during the inhibition refractory period.
Furthermore, in accordance with another preferred embodiment of the present invention, the sensing of the second step of sensing at the second site starts after the end of a refractory time period. The refractory period begins at the time of detection of the first electrical depolarization event and has a refractory period duration.
Furthermore, in accordance with another preferred embodiment of the present invention, the method further includes the step of pacing the heart by applying at least one pacing pulse to the heart through the first electrode. The refractory period prevents the sensing of electrical artifact signals by the second electrode due to the pacing pulse.
Furthermore, in accordance with another preferred embodiment of the present invention, the first site is located in or about the right ventricle of the heart and the second site is located in or about the left ventricle of the heart.
Furthermore, in accordance with another preferred embodiment of the present invention, the first site is located in or about the right atrium of the heart and the second site is located in or about the left ventricle of the heart.
Furthermore, in accordance with another preferred embodiment of the present invention, the method further includes the step of pacing the heart by applying within the beat cycle a pacing pulse to at least one of the electrodes prior to second step of applying.
Furthermore, in accordance with another preferred embodiment of the present invention, the first site is located in or about the right ventricle of the heart and the at least second site is located in or about the left ventricle of the heart.
Furthermore, in accordance with another preferred embodiment of the present invention, the step of pacing includes pacing the right ventricle by applying a pacing pulse to the first electrode or to one of the electrodes applied to the right ventricle.
Furthermore, in accordance with another preferred embodiment of the present invention, the step of pacing includes pacing the left ventricle by applying a pacing pulse to the second electrode or to one of the electrodes applied to the left ventricle.
Furthermore, in accordance with another preferred embodiment of the present invention, the step of pacing includes pacing the right atrium of the heart by delivering a pacing pulse to the right atrium through one of the electrodes applied to the right atrium.
Furthermore, in accordance with another preferred embodiment of the present invention, the first site is located in or about the right atrium of the heart and the second site is located in or about the left ventricle of the heart.
Furthermore, in accordance with another preferred embodiment of the present invention, the step of pacing includes pacing the right atrium by applying a pacing pulse to the first electrode or to one of the electrodes applied to the right atrium.
Furthermore, in accordance with another preferred embodiment of the present invention, the step of pacing includes pacing the left ventricle by applying a pacing pulse to the second electrode or to one of the electrodes applied to the left ventricles.
Furthermore, in accordance with another preferred embodiment of the present invention, the step of pacing includes pacing the right ventricle of the heart by delivering a pacing pulse to the right ventricle through one of the electrodes applied to the right ventricle.
Furthermore, in accordance with another preferred embodiment of the present invention, the detecting of at least one of the first step of sensing and the second step of sensing includes detecting a depolarization event using an event detection method selected from a threshold crossing detection method, a detection method based on one or more morphological parameters of the electrical activity, a slope based detection method and any combination thereof.
Furthermore, in accordance with another preferred embodiment of the present invention, the first electrical depolarization event is an electrical depolarization wave initiated by the intrinsic pacing activity of the heart or by a pacing pulse delivered to the heart through one of the electrodes.
Furthermore, in accordance with another preferred embodiment of the present invention, the second electrical depolarization event is an electrical depolarization wave initiated by the intrinsic pacing activity of the heart or by a pacing pulse delivered to the heart through one of the electrodes.
Furthermore, in accordance with another preferred embodiment of the present invention, the applying of the non-excitatory signal of the second step of applying is performed through the second electrode.
Furthermore, in accordance with another preferred embodiment of the present invention, the applying of the step of applying is performed in response to the earliest occurring electrical depolarization event of the at least second electrical depolarization event detected within the alert window period.
Furthermore, in accordance with another preferred embodiment of the present invention, the method further including the step of initiating an alert refractory period in response to the detection of the earliest occurring electrical depolarization event. The alert refractory period starts at the time of detection of the earliest occurring electrical depolarization event and has a third duration. The alert refractory period ends within the duration of the beat cycle. During the alert refractory period, the sensing and the detecting of the second step of detecting at the second site are disabled.
Furthermore, in accordance with another preferred embodiment of the present invention, the third duration of the alert refractory period is a preset value.
Furthermore, in accordance with another preferred embodiment of the present invention, the third duration of the alert refractory period is larger than the sum of the first duration, the second delay and the maximal allowable duration of the non-excitatory signal.
There is further provided, in accordance with another preferred embodiment of the present invention, a method for timing the delivery of a non-excitatory signal to a heart within a cardiac beat cycle. The method includes the steps of sensing electrical activity in at least a first site of the heart through at least a first electrode applied to the first site for detecting a first electrical depolarization event within the beat cycle, sensing electrical activity in at least a second site of the heart through at least a second electrode applied to the second site for detecting at least a second electrical depolarization event within the beat cycle, and applying the non-excitatory signal at or in the vicinity of the second site of the heart in response to detecting the second electrical depolarization event within an alert window period. The alert window period starts at a first delay from the time of detection of the first electrical depolarization event and has a first duration. The applying is delayed from the time of detecting of the second electrical depolarization event.
Furthermore, in accordance with another preferred embodiment of the present invention, the method further includes the step of inhibiting the applying of the non-excitatory signal of the step of applying in response to detecting at the second site a third electrical depolarization event preceding the second electrical depolarization event. The third electrical depolarization event is detected within an inhibition window period. The inhibition window period starts at a second delay from the time of detection of the first electrical depolarization event, and terminates at or before the time of starting of the alert window period. The second delay is smaller than the first delay.
Furthermore, in accordance with another preferred embodiment of the present invention, the step of inhibiting includes the step of initiating an inhibition refractory period. The inhibition refractory period starts at the time of detecting of the third electrical depolarization event and has a second duration. The sensing of the electrical activity in the second site is disabled during the inhibition refractory period.
Furthermore, in accordance with another preferred embodiment of the present invention, the second duration of the inhibition refractory period is a preset duration.
Furthermore, in accordance with another preferred embodiment of the present invention, the second duration of the inhibition refractory period is equal to or larger than the value obtained by summing the inhibition window period, the first duration, the second delay and the maximal allowable duration of the non-excitatory signal.
Furthermore, in accordance with another preferred embodiment of the present invention, the step of initiating includes the step of determining the value of the second duration for the beat cycle from the time of detecting of the third electrical depolarization event within the beat cycle and from the preset values of the first duration of the alert window, the first delay and the maximal allowable duration of the non-excitatory signal.
Furthermore, in accordance with another preferred embodiment of the present invention, the second duration is larger than the value obtained by subtracting the time of detecting of the third electrical depolarization event from the sum of the first delay, the first duration, the second delay and the maximal allowable duration of the non-excitatory signal.
Furthermore, in accordance with another preferred embodiment of the present invention, the first site is located in or about the right ventricle of the heart and the second site is located in or about the left ventricle of the heart.
Furthermore, in accordance with another preferred embodiment of the present invention, the first site is located in or about the right atrium of the heart and the second site is located in or about the left ventricle of the heart.
Furthermore, in accordance with another preferred embodiment of the present invention, the method further includes the step of pacing the heart within the beat cycle by delivering a pacing pulse to the heart prior to the step of applying.
Furthermore, in accordance with another preferred embodiment of the present invention, the delivering of the pacing pulse includes applying the pacing pulse to an electrode selected from the first electrode, the second electrode and a third electrode applied to a third site of the heart.
Furthermore, in accordance with another preferred embodiment of the present invention, the first site is located in or about the right ventricle of the heart and the second site is located in or about the left ventricle of the heart.
Furthermore, in accordance with another preferred embodiment of the present invention, the step of pacing includes pacing the right ventricle by applying a pacing pulse to the first electrode or to a pacing electrode applied to the right ventricle.
Furthermore, in accordance with another preferred embodiment of the present invention, the step of pacing includes pacing the left ventricle by applying a pacing pulse to the second electrode or to a pacing electrode applied to the left ventricle.
Furthermore, in accordance with another preferred embodiment of the present invention, the step of pacing includes pacing the right atrium of the heart by delivering a pacing pulse to the right atrium through a third electrode applied to the right atrium.
Furthermore, in accordance with another preferred embodiment of the present invention, the first site is located in or about the right atrium of the heart and the second site is located in or about the left ventricle of the heart.
Furthermore, in accordance with another preferred embodiment of the present invention, the first electrode is applied to the right atrium of the heart, the second electrode is applied to the left ventricle of the heart and the third electrode is applied to the right atrium of the heart.
Furthermore, in accordance with another preferred embodiment of the present invention, the first electrode is applied the right atrium of the heart, the second electrode is applied to the left ventricle of the heart and the third site is the right ventricle of the heart.
Furthermore, in accordance with another preferred embodiment of the present invention, the method further includes the step of pacing the heart by delivering a pacing pulse to the heart prior to said step of applying through at least one electrode selected from the first electrode, the second electrode and a third electrode applied to a third site of the heart.
Furthermore, in accordance with another preferred embodiment of the present invention, the first site is located in or about the right ventricle of the heart, the second site is located in or about the left ventricle of the heart and the third site is the right atrium of the heart.
Furthermore, in accordance with another preferred embodiment of the present invention, the detecting of at least one of the first step of sensing and the second step of sensing includes detecting a depolarization event using an event detection method selected from a threshold crossing detection method, a detection method based on one or more morphological parameters of the electrical activity, a slope based detection method, and any combination thereof.
Furthermore, in accordance with another preferred embodiment of the present invention, the first electrical depolarization event is an electrical depolarization wave initiated by the intrinsic pacing activity of the heart or by a pacing pulse delivered to the heart.
Furthermore, in accordance with another preferred embodiment of the present invention, the second electrical depolarization event is an electrical depolarization wave initiated by the intrinsic pacing activity of the heart or by a pacing pulse.
Furthermore, in accordance with another preferred embodiment of the present invention, the applying of the non-excitatory signal of the step of applying is performed through the second electrode of the second step of sensing.
Furthermore, in accordance with another preferred embodiment of the present invention, the applying of the step of applying is performed in response to the detection of the earliest of the at least second electrical depolarization event detected within the alert window period.
Furthermore, in accordance with another preferred embodiment of the present invention, the method further includes the step of initiating an alert refractory period in response to the detection of the earliest occurring electrical depolarization event within the alert window period. The alert refractory period starts at the time of detection of the earliest occurring electrical depolarization event and has a third duration. The alert refractory period ends within the duration of the beat cycle. During the alert refractory period the sensing and the detecting of the second step of detecting at the second site are disabled.
Furthermore, in accordance with another preferred embodiment of the present invention, the third duration of the alert refractory period is a preset value.
Furthermore, in accordance with another preferred embodiment of the present invention, the third duration of the alert refractory period is larger than the sum of the first duration, the second delay and the maximal allowable duration of the non-excitatory signal.
There is further provided, in accordance with another preferred embodiment of the present invention, apparatus for timing the delivery of a non-excitatory signal to the heart within a cardiac beat cycle of the heart. The apparatus includes a plurality of electrodes adapted to be implanted in the heart. The apparatus also includes an excitable tissue control unit operatively connected to at least one of the plurality of electrodes for delivering the non-excitatory signal to the heart. The apparatus further includes a detecting unit operatively connected to a first electrode of the plurality of electrodes for sensing electrical activity in a first cardiac site and for detecting a first electrical depolarization event within the beat cycle. The detection unit is also connected to a second electrode of the plurality of electrodes for sensing electrical activity in a second cardiac site and for detecting at least a second electrical depolarization event within the beat cycle. The apparatus also includes a controller unit operatively connected to the excitable tissue control unit and the detection unit for controlling the operation of the excitable tissue control unit and the detection unit, for receiving from the detection unit signals representing the detection of the first electrical depolarization event and the second electrical depolarization event and for controlling the delivery, through at least one of the plurality of electrodes, of the non-excitatory signal to the second cardiac site or in the vicinity thereof in response to the detecting of the second electrical depolarization event by the detection unit within an alert window period. The alert window period starts at a first delay from the time of detection of the first electrical depolarization event and has a first duration. The applying is delayed from the time of detecting of the second electrical depolarization event. The apparatus also includes a power source for providing power to the excitable tissue control unit, the detection unit and the controller unit.
Furthermore, in accordance with another preferred embodiment of the present invention, the controller is adapted to inhibit the applying of the non-excitatory signal in response to receiving from the detecting unit a signal representing the detecting at the second site of a third electrical depolarization event preceding the second electrical depolarization event. The third electrical depolarization event is detected within an inhibition window period. The inhibition window period starts at a second delay from the time of detection of the first electrical depolarization event and terminates at or before the time of starting of the alert window period. The second delay is smaller than the first delay.
Furthermore, in accordance with another preferred embodiment of the present invention, the controller is adapted for initiating an inhibition refractory period. The inhibition refractory period is initiated by the signal representing the detecting at the second site of the third electrical depolarization event by the detection unit. The inhibition refractory period has a second duration. The controller is adapted for disabling the sensing by the detecting unit of the electrical activity in the second site during the inhibition refractory period.
Furthermore, in accordance with another preferred embodiment of the present invention, the second duration of the inhibition refractory period is a preset duration.
Furthermore, in accordance with another preferred embodiment of the present invention, the second duration of the inhibition refractory period is equal to or larger than the value obtained by summing the inhibition window period, the first duration, the second delay and the maximal allowable duration of the non-excitatory signal.
Furthermore, in accordance with another preferred embodiment of the present invention, the controller is adapted to determine the value of the second duration for the inhibition refractory period from the time of detecting of the third electrical depolarization event within the beat cycle and from the preset values of the first duration of the alert window, the first delay and the maximal allowable duration of the non-excitatory signal.
Furthermore, in accordance with another preferred embodiment of the present invention, the second duration is larger than the value obtained by subtracting the time of detecting of the third electrical depolarization event from the sum of the first delay, the first duration, the second delay and the maximal allowable duration of the non-excitatory signal.
Furthermore, in accordance with another preferred embodiment of the present invention, the detecting unit is adapted for detecting at least one of the first electrical depolarization event and the second electrical depolarization event by using an event detection method selected from a threshold crossing detection method, a detection method based on one or more morphological parameters of the electrical activity, a slope based detection method, and any combination thereof.
Furthermore, in accordance with another preferred embodiment of the present invention, the detecting unit is selected from an analog detecting unit and a digital detecting unit.
Furthermore, in accordance with another preferred embodiment of the present invention, the controller unit is selected from a central processing unit, a micro-controller unit, a digital signal processing unit, a computer, a workstation, and any combination thereof.
Furthermore, in accordance with another preferred embodiment of the present invention, the apparatus further includes an implantable housing. The power unit, the detecting unit, the excitable tissue control unit and the controller unit are contained within the housing.
Furthermore, in accordance with another preferred embodiment of the present invention, the apparatus further includes a telemetry unit disposed within the housing and operatively connected to the controller.
Furthermore, in accordance with another preferred embodiment of the present invention, the plurality of electrodes is implanted within the patient, and the excitable tissue control unit, the detecting unit, the controller unit and the power unit are disposed outside of the patient.
Furthermore, in accordance with another preferred embodiment of the present invention, the first electrode is implanted in or about the right ventricle of the heart and the second electrode is implanted in or about the left ventricle of the heart.
Furthermore, in accordance with another preferred embodiment of the present invention, the first electrode is implanted in or about the right atrium of the heart and the second site is located in or about the left ventricle of the heart.
Furthermore, in accordance with another preferred embodiment of the present invention, the apparatus further includes a pacing unit powered by the power source and operatively connected to at least one of the plurality of electrodes for delivering pacing pulses to the heart. The controller unit is operatively connected to the pacing core unit for controlling the operation thereof.
Furthermore, in accordance with another preferred embodiment of the present invention, the first electrode is implanted in or about the right ventricle of the heart and the second electrode is implanted in or about the left ventricle of the heart.
Furthermore, in accordance with another preferred embodiment of the present invention, the first electrode is operatively connected to the pacing unit for pacing the right ventricle.
Furthermore, in accordance with another preferred embodiment of the present invention, the second electrode is operatively connected to the pacing unit for pacing the left ventricle.
Furthermore, in accordance with another preferred embodiment of the present invention, at least one electrode of the plurality of electrodes is operatively connected to the pacing unit and is implanted in or about the right atrium for pacing the right atrium.
Furthermore, in accordance with another preferred embodiment of the present invention, the first electrode is implanted in or about the right atrium of the heart and the second electrode is implanted in or about the left ventricle of the heart.
Furthermore, in accordance with another preferred embodiment of the present invention, the first electrode is operatively connected to the pacing unit for pacing the right atrium.
Furthermore, in accordance with another preferred embodiment of the present invention, the second electrode is operatively connected to the pacing unit for pacing the left ventricle.
Furthermore, in accordance with another preferred embodiment of the present invention, at least one of the electrodes is implanted in or about the right ventricle of the heart and is operatively connected to the pacing unit for pacing the right ventricle.
Furthermore, in accordance with another preferred embodiment of the present invention, the controller is adapted to control the excitable tissue control unit to deliver the non-excitatory signal in response to the detection of the earliest electrical depolarization event of the second electrical depolarization event within the alert window period.
Furthermore, in accordance with another preferred embodiment of the present invention, the controller is adapted to initiate an alert refractory period in response to the detection of the earliest electrical depolarization event within the alert window period. The alert refractory period starts at the time of detection of the earliest electrical depolarization event within the alert window period and has a third duration. The alert refractory period ends within the duration of the beat cycle. During the alert refractory period, the sensing and the detecting of the detecting unit is disabled.
Furthermore, in accordance with another preferred embodiment of the present invention, the third duration of the alert refractory period is a preset value.
Finally, in accordance with another preferred embodiment of the present invention, the third duration of the alert refractory period is larger than the sum of the first duration, the second delay and the maximal allowable duration of the non-excitatory signal.